Immune Complex-mediated Glomerulonephritis Research Articles

HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.

Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis

IntroductionAround 50% of C3 glomerulopathy and primary immune-complex-mediated membranoproliferative glomerulonephritis (C3G, IC-MPGN) patients reach kidney failure at 10 years after diagnosis. Since these patients are generally young, the majority will be listed for kidney transplantation. However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, as they are mainly based on retrospective monocentric studies. We thus aimed to provide detailed multicenter data on these patients, taking advantage of the ongoing nationwide Swiss Transplant Cohort Study. MethodsWe analyzed patient and graft outcome, including the risk of graft loss in relation to recurrence of glomerulopathy. ResultsForty-one (10 C3G, 31 IC-MPGN) transplanted recipients were included with a mean age at transplantation of 48+16 years. Living donation provided 53% of the organs. During a mean follow-up of 4.7 years, 7 patients (4 C3G, 3 IC-MPGN) presented disease recurrence with a mean time to recurrence of 1.2 years. New-onset or rapidly increasing proteinuria was an early marker of recurrence, preceding significant decline in eGFR. Following recurrence, 28% lost their graft, compared to 11% of patients without recurrence. Disease recurrence was the primary cause of graft loss in all patients. Finally, 14% of patients died during follow-up. ConclusionThis study provides important insights into the epidemiology and outcome of C3G and IC-MPGN patients and their grafts after kidney transplantation. The data also suggest that proteinuria may serve as an early biomarker of disease recurrence and should be considered in patient management as well as an endpoint in current clinical trials using novel complement modulators.

ACE in Neutrophils Ameliorates Glomerular Damage in Immune Complex-Mediated Crescentic Glomerulonephritis via Complement C3 and C and N Domains of ACE

ACE in Neutrophils Ameliorates Glomerular Damage in Immune Complex-Mediated Crescentic Glomerulonephritis via Complement C3 and C and N Domains of ACE

A New Era for PET/CT: Applications in Non-Tumorous Renal Pathologies.

Non-tumorous kidney diseases include a variety of conditions affecting both the structure and function of the kidneys, thereby causing a range of health-related problems. Positron emission tomography/computed tomography (PET/CT) has emerged as a potential diagnostic tool, offering a multifaceted approach to evaluating non-tumorous kidney diseases. Its clinical significance extends beyond its conventional role in cancer imaging, enabling a comprehensive assessment of renal structure and function. This review explores the diverse applications of PET/CT imaging in the evaluation of non-cancerous kidney diseases. It examines PET/CT's role in assessing acute kidney injuries, including acute pyelonephritis and other forms of nephritis, as well as chronic conditions such as immune complex-mediated glomerulonephritis and chronic kidney disease. Additionally, the review delves into PET/CT's utility in evaluating complications in renal transplant recipients, identifying renal histiocytosis and detecting renal amyloidosis. The current review aims to promote further research and technological advancements to popularize PET/CT's clinical utility in diagnosing and treating non-tumorous kidney diseases.

Lupus-like manifestations after allogenic hematopoietic stem cell transplantation: a rarecase of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

Immune Complex-Mediated Membranoproliferative Glomerulonephritis Secondary to Primary Biliary Cholangitis: A Rare Case Report

Immune Complex-Mediated Membranoproliferative Glomerulonephritis Secondary to Primary Biliary Cholangitis: A Rare Case Report

Kidney involvement in myelodysplastic syndromes.

The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9g/g, and median serum creatinine was 3.2mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

#726 The ugly face of shunt nephritis

Abstract Background and Aims Shunt nephritis is a rare immune complex-mediated reversible glomerulonephritis due to infected ventricular shunts, most commonly ventriculo-peritoneal shunts (VP) for the treatment of hydrocephalus. Although infection of CSF is common, shunt nephritis is rare, however remains a life-threatening disorder with a high possibility of the development of glomerulonephritis (GN), chronic kidney disease (CKD) & death. Antibiotic treatment alone is generally ineffective in resolution of GN, but removal of the shunt is usually, associated with improvement of the renal disease. Method We have reported four cases with shunt-nephritis that had occurred in consequence of infected VP shunt for treatment of hydrocephalus. The clinical courses, immunological, and histological findings were different in the reported cases, however the same management by removal of the shunt system led to an improvement of the laboratory parameters & clinical symptoms in 3 patients. Results The 1st case was a 10 -year-old boy who had VP shunt (inserted at the age of 5, for managing post meningoencephalitis hydrocephalus), came with acute kidney injury (AKI) without recent proceeding infection. Renal biopsy revealed picture of membranoproliferative GN (MPGN), however his initial CSF analysis was −ve for infection, however, 4 months later, repeat CSF culture was +ve for Propionibacterium acnes. The patient was admitted for shunt removal & 1 month course of antibiotic. AKI & GN improved with normalization of C3 after 2 months. The 2nd case was 15-year-old girl with VP shunt at age of 9 months due to congenital hydrocephalus, who came with shunt dysfunction, AKI, high fever & hematuria. CSF analysis was +ve for staphylococcus coagulase & staphylococcus aureus, where a 1 month course of antibiotic hadn't improve the symptoms. Renal biopsy showed MPGN. Shunt removal with insertion of new one, was associated with marked improvement of AKI with normalization of complement levels. The 3rd case was a 7-year-old girl who came with picture of sepsis, and convulsions. She had VP shunt inserted since the age of 3 months as a consequence of neonatal sepsis & intracranial hemorrhage. She had AKI & consumed C3. CSF analysis revealed streptococcal pneumonia. Renal biopsy showed diffused proliferative GN with 50% crescentic formation. Patient needed parenteral antibiotic course for 14 days, twice hemodialysis session & pulse steroid without improvement, however shunt removal & insertion of new one was associated with marked improvement of symptoms, and she diagnosed as shunt nephritis. The 4th case was 18-year-old female with came with manifestation of increased intracranial pressure, and fever of 1 month duration. She had VP shunt because of traumatic intraventricular hemorrhage at age of 7. Initial investigations revealed sepsis, AKI & consumed C3. Antibiotic couldn't manage her AKI. Renal biopsy showed MPGN. CSF analysis was +ve for coagulase-negative Staphylococcus. VP shunt was removed & 1 month course of antibiotic was given without improvement of her AKI and she turned into CDK stage 3. Conclusion The importance of regular observation & narrow-interval follow-up investigations for early recognition of this reversible form of glomerulonephritis is emphasized.

#1640 Alternative complement pathway disorders in the transplant setting—experience from a large volume center

Abstract Background and Aims Complement alternative pathway disorders, atypical hemolytic-uremic syndrome (aHUS) and C3 glomerulopathy (C3G), are rare diseases with a high rate of recurrence after kidney transplantation. Due to limited availability of testing, patients may go undiagnosed, indicating testing during pretransplant evaluation. Posttransplant thrombotic microangiopathy (TMA) is a rare complication of transplantation. A large number of post transplant TMAs is regarded as secondary, either to immunosuppressive drugs or transplant itself. In select cases, complement alternative pathway disorders analysis is warranted. Method We retrospectively reviewed all patients in whom complement system diagnostic work-up was performed in the transplant setting in our center, from 2017 to 2022. Complement system analysis in isolated histological TMA of the allograft, without extrarenal manifestations and with known cause of native kidneys ESRD, was not performed routinely. Patients in whom alternative pathway disorders were confirmed were compared with those with no abnormalities detected by complement system analysis. Results 12 patients were identified, 75% male, median age 39.5 years (IQR 28-60.25). 8 patients were evaluated before transplantation. 4 of the 8 patients were referred for transplantation with diagnosed aHUS. Genetic testing was used for recurrence risk stratification. In living donor transplantations 2 donors were tested as well. One patient was referred from a neighboring resource poor country and was not on eculizumab therapy. He was homozygous for a high risk causative mutation. He was declined for living related donor kidney transplant, due to risk to the donor and unavailability of eculizumab. Compassionate use request was initiated. One patient was referred as possible C3G and repeat complement analysis revealed elevated C3Nef. Out of 3 patients, previously diagnosed as CKD of unknown origin or immune complex-mediated membranoproliferative glomerulonephritis, 2 were diagnosed during pretransplant evaluation: one as C3G and the other as aHUS. 4 patients were evaluated posttransplant. One analysis was performed due to recurrent C3G of the allograft, with confirmed competent dysregulation. 2 analyses were in liver transplant recipients, both with systemic TMA. Severe overactivation with consumption of complement was proven in one and treated with eculizumab. The characteristics of patients with diagnosed disorders of the complement system and those without are shown in Table 1. Conclusion Transplant physicians should keep a high volume of suspicion for complement dysregulation disorders, both during the pretransplant work-up and when evaluating TMA and recurrent GN posttransplant. Special caution should be advised when a patient is referred as chronic GN, MPGN or unknown cause ESKD at a young age.

Hydralazine use can be associated with IgM-dominated immune complex-mediated glomerulonephritis

ABSTRACT Context IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine. Design Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail. Results Patients’ ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases. Conclusion The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.

MicroRNA-126 in dogs with immune complex-mediated glomerulonephritis.

Most proteinuric dogs with naturally occurring chronic kidney disease have amyloidosis (AMYL), glomerulosclerosis (GS), or immune complex-mediated glomerulonephritis (ICGN), each with different treatment and prognosis. A noninvasive and disease-specific biomarker is lacking. We hypothesized that the expression pattern of biofluid microRNA (miRNAs and miRs) would correlate with disease progression and categorization. Archived serum and urine samples from 18 dogs with glomerular disease and 6 clinically healthy dogs; archived urine samples from 49 dogs with glomerular disease and 13 clinically healthy dogs. Retrospective study. Archived biofluid samples from adult dogs with biopsy-confirmed glomerular disease submitted to the International Veterinary Renal Pathology Service between 2008 and 2016 were selected. Serum and urinary miRNAs were isolated and profiled using RNA sequencing. Urinary miR-126, miR-21, miR-182, and miR-486 were quantified using quantitative reverse transcription PCR. When comparing more advanced disease with earlier disease, no serum miRNAs were differentially expressed, but urinary miR-21 and miR-182 were 1.63 (95% CI: .86-3.1) and 1.45 (95% CI: .82-2.6) times higher in azotemic dogs, respectively (adjusted P < .05) and weakly correlated with tubulointerstitial fibrosis (miR-21: r = .32, P = .03; miR-182: r = .28, P = .05). Expression of urinary miR-126 was 10.5 (95% CI: 4.1-26.7), 28.9 (95% CI: 10.5-79.8), and 126.2 (95% CI: 44.7-356.3) times higher in dogs with ICGN compared with dogs with GS, AMYL, and healthy controls, respectively (P < .001). The miR-126 could help identify dogs that might benefit from immunosuppressive therapy in the absence of a biopsy. MiR-21 and miR-182 are potential markers of disease severity and fibrosis.

Three Diseases Mediated by Different Immunopathologic Mechanisms-ANCA-Associated Vasculitis, Anti-Glomerular Basement Membrane Disease, and Immune Complex-Mediated Glomerulonephritis-A Common Clinical and Histopathologic Picture: Rapidly Progressive Crescentic Glomerulonephritis.

Immune mechanisms play an important role in the pathogenesis of glomerulonephritis (GN), with autoimmunity being the main underlying pathogenetic process of both primary and secondary GN. We present three autoimmune diseases mediated by different autoimmune mechanisms: glomerulonephritis in vasculitis mediated by anti-neutrophil cytoplasmic antibodies (ANCAs), glomerulonephritis mediated by anti-glomerular basement membrane antibodies (anti-GBM antibodies), and immune complex-mediated glomerulonephritis. Some of these diseases represent a common clinical and histopathologic scenario, namely rapidly progressive crescentic glomerulonephritis. This is a severe illness requiring complex therapy, with the main role being played by therapy aimed at targeting immune mechanisms. In the absence of immune therapy, the crescents, the characteristic histopathologic lesions of this common presentation, progress toward fibrosis, which is accompanied by end-stage renal disease (ESRD). The fact that three diseases mediated by different immunopathologic mechanisms have a common clinical and histopathologic picture reveals the complexity of the relationship between immunopathologic mechanisms and their clinical expression. Whereas most glomerular diseases progress by a slow process of sclerosis and fibrosis, the glomerular diseases accompanied by glomerular crescent formation can progress, if untreated, in a couple of months into whole-nephron glomerulosclerosis and fibrosis. The outcome of different immune processes in a common clinical and histopathologic phenotype reveals the complexity of the relationship of the kidney with the immune system. The aim of this review is to present different immune processes that lead to a common clinical and histopathologic phenotype, such as rapidly progressive crescentic glomerulonephritis.

An Atypical Case of Immune Complex-Mediated Glomerulonephritis

An Atypical Case of Immune Complex-Mediated Glomerulonephritis

Lupus Nephritis in Children: Novel Perspectives.

Childhood-onset systemic lupus erythematosus is an inflammatory and autoimmune condition characterized by heterogeneous multisystem involvement and a chronic course with unpredictable flares. Kidney involvement, commonly called lupus nephritis, mainly presents with immune complex-mediated glomerulonephritis and is more frequent and severe in adults. Despite a considerable improvement in long-term renal prognosis, children and adolescents with lupus nephritis still experience significant morbidity and mortality. Moreover, current literature often lacks pediatric-specific data, leading clinicians to rely exclusively on adult therapeutic approaches. This review aims to describe pediatric lupus nephritis and provide an overview of the novel perspectives on the pathogenetic mechanisms, histopathological classification, therapeutic approach, novel biomarkers, and follow-up targets in children and adolescents with lupus nephritis.

Genetic investigation of Nordic patients with complement-mediated kidney diseases.

Complement activation in atypical hemolytic uremic syndrome (aHUS), C3 glomerulonephropathy (C3G) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) may be associated with rare genetic variants. Here we describe gene variants in the Swedish and Norwegian populations. Patients with these diagnoses (N=141) were referred for genetic screening. Sanger or next-generation sequencing were performed to identify genetic variants in 16 genes associated with these conditions. Nonsynonymous genetic variants are described when they have a minor allele frequency of <1% or were previously reported as being disease-associated. In patients with aHUS (n=94, one also had IC-MPGN) 68 different genetic variants or deletions were identified in 60 patients, of which 18 were novel. Thirty-two patients had more than one genetic variant. In patients with C3G (n=40) 29 genetic variants, deletions or duplications were identified in 15 patients, of which 9 were novel. Eight patients had more than one variant. In patients with IC-MPGN (n=7) five genetic variants were identified in five patients. Factor H variants were the most frequent in aHUS and C3 variants in C3G. Seventeen variants occurred in more than one condition. Genetic screening of patients with aHUS, C3G and IC-MPGN is of paramount importance for diagnostics and treatment. In this study, we describe genetic assessment of Nordic patients in which 26 novel variants were found.

42 APPARENT: A multicenter, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy and safety of iptacopan in idiopathic (primary) immune complex-mediated membranoproliferative glomerulonephritis

42 APPARENT: A multicenter, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy and safety of iptacopan in idiopathic (primary) immune complex-mediated membranoproliferative glomerulonephritis

Histopathological Subtypes of Primary Nephrotic Syndrome in Paediatric Patients at the University Teaching Hospital in Lusaka, Zambia

Background: Minimal change disease (MCD) has been shown to be a common histological presentation in children presenting with nephrotic syndrome (NS) in developed countries. In Africa, information on clinical and histological characteristics of paediatric NS is scarce. This study assessed the characteristics and histological subtypes of NS.&#x0D; Methods: This was a prospective study that consecutively indexed children aged 2-16 years with the diagnosis of NS who were referred to the largest tertiary teaching hospital, Lusaka, Zambia. Thirteen children presenting with NS were biopsied under ultrasound guidance after ethical approval. The primary outcome of the study was to describe the histological characteristics of paediatric NS.&#x0D; Results: Thirteen children of African descent with a median age of onset of NS of 9.25 years (2.0-15.0) were enrolled in the study. The histopathologic lesions were as follows; four had MCD, four had focal segmental glomerulosclerosis (FSGS), one had immune complex mediated glomerulonephritis (ICMN) and four were inconclusive. Haematuria was present in eight out of 13 patients (61.5%) and hypertension was present in five of 13 patients (38.0%). Three children did not have either haematuria or hypertension. Ten of the 13 participants had primary steroid resistance. &#x0D; Conclusion: This study has demonstrated the need to perform a pre-treatment renal biopsy in paediatric patients presenting with NS in view of the atypical presentation, variable histopathologic findings, and unpredictable response to steroid therapy.

#2663 KIDNEY INVOLVEMENT IN MYELODYSPLASTIC SYNDROMES

Abstract Background and Aims Myelodysplastic syndromes (MDS) are hematologic disorders characterized by ineffective and dysplastic hematopoiesis that can be associated with systemic inflammatory and autoimmune diseases. The objective of this study was to describe kidney involvement in MDS patients, their treatments, and outcomes. Method We conducted a French and American multicenter retrospective observational study in nine centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Seventeen patients (males n = 11, median age 76 [70-79]) developed a kidney disease 6 months [0-31] after the diagnosis of MDS. Median urinary protein to creatinine ratio was 1.9g/g [0.8-3.3], and median serum creatinine was 3.5mg/dL [1.5-4.7]. Twelve patients (70%) had AKI at presentation, and 14 (82%) extra-renal symptoms, which consisted mostly in cutaneous and pneumological manifestations. The renal diagnoses included antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) (n = 8, 47%), ANCA negative vasculitis (n = 4, 24%), C3 glomerulonephritis (n = 2), immune complex-mediated glomerulonephritis (n = 1), polyarteritis nodosa (n = 1), and IgA vasculitis (n = 1). Kidney biopsies were performed in 10 of the cases. All patients, except one, received a treatment following the MDS-associated kidney injury (n = 16, 94% with steroids). The effect of MDS treatment on kidney injury could be assessed in 8 patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 9 months [4.1-14.2], 4 patients had CKD stage 3, 4 CKD stage 4, 5 an end stage kidney disease. Three patients evolved to an acute myeloid leukemia (AML), and 3 died. Compared to 84 MDS controls, patients who had a kidney involvement were younger (p = 0.03), had a higher number of dysplasia lineages (3 lineages, p = 0.001), and were more eligible to receive hypomethylating agents (p = 0.031), but no survival difference was seen between the two groups (p = 0.5227). Compared to 265 AAV without MDS, MDS-associated AAV were older (p = 0.019), ANCA serology was more frequently negative (p = 0.014), and more cutaneous lesions were seen (p = 0.003). Conclusion The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis, and especially AAV. A diagnosis of ANCA vasculitis in an elderly patient, or with a cutaneous manifestation, or without ANCA positivity, should lead to the search for a possible MDS.

Utility of C4d Immunohistochemistry as an Adjunct Stain in Diagnostic Renal Pathology of Glomerular Diseases.

C4d is a byproduct of the activation of the classic and lectin complement pathways. Being routinely used as a marker for antibody-mediated rejection, the significance of C4d in native kidney disease is currently being widely studied. We evaluated glomerular and extraglomerular C4d staining in 82 biopsies of proliferative and nonproliferative glomerulonephritis diagnosed in our institution. The staining pattern of C4d was tabulated in various glomerular diseases. All biopsies of membranous nephropathy including membranous lupus nephritis (Class V) and immune complex-mediated membranoproliferative glomerulonephritis (MPGN) consistently showed C4d deposits along glomerular basement membrane mirroring the location of immunoglobulin and complement in these conditions. Conversely, other glomerular diseases like IgA nephropathy, postinfectious glomerulonephritis, focal segmental glomerulosclerosis, minimal change disease, and diabetic nephropathy showed variable mesangial and capillary wall C4d deposits. To summarize, the consistent pattern of C4d staining in membranous nephropathy (primary and secondary)and immune complex-mediated MPGN can be used as a valuable adjunct tool in establishing the diagnosis, especially when immunofluorescence findings are limited by inadequate sampling.C4d reactivity in other glomerular diseases are variable and may not aid as a diagnostic tool in renal biopsy evaluation.

The leukotriene B4 receptors BLT1 and BLT2 as potential therapeutic targets.

Leukotriene B4 (LTB4 ) was recognized as an arachidonate-derived chemotactic factor for inflammatory cells and an important drug target even before the molecular identification of its receptors. We cloned the high- and low-affinity LTB4 receptors, BLT1 and BLT2, respectively, and examined their functions by generating and studying gene-targeted mice. BLT1 is involved in the pathogenesis of various inflammatory and immune diseases, including asthma, psoriasis, contact dermatitis, allergic conjunctivitis, age-related macular degeneration, and immune complex-mediated glomerulonephritis. Meanwhile, BLT2 is a high-affinity receptor for 12-hydroxyheptadecatrienoic acid, which is involved in the maintenance of dermal and intestinal barrier function, and the acceleration of skin and corneal wound healing. Thus, BLT1 antagonists and BLT2 agonists are promising candidates in the treatment of inflammatory diseases.